Work with LifeSpan to design a custom immunohistochemistry to address your specific biological question. Outsource the entire localization process without having to
worry about finding and characterizing target specific antibodies, sourcing and validating difficult-to-find tissues, and having the ability to interpret the resulting
immunostaining in relation to complex human pathologies.
TCR Screening Services
Test your therapeutic antibodies in immunohistochemistry against a broad panel of normal frozen human tissue types in order to determine potential unintended binding.
Our non-GLP TCR services are designed on the FDA recommendation outlined in their "Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use".
Description: Angiotensin II is a hormone that plays an important role in regulating blood pressure. Elevated levels of angiotensin II are implicated in inducing and maintaining hypertension, and also in the development of atherosclerosis. Both of these effects are mediated by the angiotensin II type 1 (AT1) receptor. Losartan is a mammalian AT1 receptor antagonist with a Ki value of 5-20 nM. In humans, losartan effectively controls hypertension while protecting renal function. Nitric oxide (NO) causes vasodilation and also inhibits platelet and neutrophil aggregation in the endothelium. NO-losartan A possesses similar anti-hypertensive effects to losartan, with the addition of the vasodilating effects of NO release.
NO-Losartan A is supplied as a crystalline solid. A stock solution may be made by dissolving the NO-losartan A in an organic solvent purged with an inert gas. NO-Losartan A is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide. The solubility of NO-losartan A in these solvents is approximately 30 mg/ml. NO-Losartan A is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, NO-losartan A should first be dissolved in ethanol and then diluted with the aqueous buffer of choice. NO-Losartan A has a solubility of approximately 0.5 mg/ml in a 1:5 solution of ethanol:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day.
Ortiz, M.C., Sanabria, E., Manriquez, M.C., et al. Role of endothelin and isoprostanes in slow pressor responses to angiotensin II. Hypertension 37(2), 505-511 (2001).
Schiffrin, E.L. Beyond blood pressure: The endothelium and atherosclerosis progression. Am. J. Hypertens 15, 115S-122S (2002).
Ji, H., Leung, M., Zhang, Y., et al. Differential structural requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor. Identification of amino acid residues that determine binding of the antihypertensive drug losartan. J. Biol. Chem. 269(24), 16533-16536 (1994).
Caruso, D., D’Avino, M., Acampora, C., et al. Effects of losartan and chlorthalidone on blood pressure and renal vascular resistance index in non-diabetic patients with essential hypertension and normal renal functions. J. Cardiovasc. Pharmacol. 44, 520-524 (2004).
Moncada, S. and Higgs, A. The L-arginine-nitric oxide pathway. N. Engl. J. Med. 329, 2002-2012 (1993).
Breschi, M.C., Calderone, V., Digiacomo, M., et al. NO-sartans: A new class of pharmacodynamic hybrids as cardiovascular drugs. J. Med. Chem. 47, 5597-5600 (2004).